The goal of this project is to improve magnetic resonance imaging (MRI) for the detection and treatment of osteoarthritis (OA). Current routine OA imaging methods only show the late changes of the disease after irreversible tissue loss has occurred. The techniques developed here will allow investigators and clinicians to track progress of the disease before tissue loss has occurred, leading to better treatments of joint injuries, faster drug discovery, and improved scientific understanding of OA progression. Relevance: MRI is widely regarded as the most sensitive method for assessing early changes due to OA. Many different MRI methods have been studied, including methods sensitive to potentially reversible changes occurring early in the disease process, but not all are practical for routine exams. Our research will develop the hardware and software necessary for the routine assessment of the earliest changes of the disease in cartilage and other joint tissues. This also will enable development and testing of treatments for this disorder. Approach: The proposed effort addresses the technical challenges to using MRI methods that are sensitive to early changes in OA. Our approach is to develop new cutting-edge methods to make MRI more sensitive to the morphological and biochemical study of OA. Specifically, we aim to (1) develop more sensitive methods of 3D imaging for quantifying the morphology of the whole knee joint, including both cartilage and other important structures, (2) develop methods for quantitative 3D imaging of cartilage glycosaminoglycan content with sodium MRI and, (3) demonstrate, in a clinical study, that our new methods are highly sensitive to early, potentially reversible changes of OA. At the end of the funding period, we will have developed and validated methods to efficiently study the progression of OA in order to improve clinical outcomes, aid development of disease-modifying therapies, and improve scientific understanding of OA.